Modulating innate immunity improves hepatitis C virus infection and replication in stem cell-derived hepatocytes.
Modulating innate immunity improves hepatitis C virus infection and replication in stem cell-derived hepatocytes.
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DOI：
10.1016/j.stemcr.2014.04.018
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发表时间：
2014-07-08
影响因子：
5.9
通讯作者：
Hay, David C.
中科院分区：
文献类型：
--
作者：
Zhou, Xiaoling;Sun, Pingnan;Lucendo-Villarin, Baltasar;Angus, Allan G. N.;Szkolnicka, Dagmara;Cameron, Kate;Farnworth, Sarah L.;Patel, Arvind H.;Hay, David C.
在这项研究中，人胚胎干细胞衍生的肝细胞（hESC-Heps）的能力，以支持丙型肝炎病毒（HCV）的感染和复制进行了研究。hESC-Heps能够支持整个病毒生命周期，包括感染性病毒体的释放。虽然支持，hESC-Hep病毒感染水平并不像在Huh 7细胞中观察到的那样大。我们推断hESC-Heps中的先天免疫应答可能导致低水平的感染和复制。在进一步的研究中，我们发现了一个强大的III型干扰素反应hESC-肝癌是由HCV引发的。有趣的是，JAK/STAT信号通路的特异性抑制导致hESC-Heps中HCV感染和复制的增加。值得注意的是，干扰素应答在Huh 7细胞中不明显。总之，我们已经建立了一个强大的基于细胞的系统，允许在体外病毒-宿主相互作用的深入研究。hESC衍生的肝细胞支持丙型肝炎病毒（HCV）感染和复制hESC衍生的肝细胞响应HCV感染激活先天免疫JAK/STAT信号传导的抑制改善HCV感染和复制研究了人胚胎干细胞衍生的肝细胞（hESC-Heps）支持丙型肝炎病毒（HCV）生命周期的能力。虽然支持，hESC-Hep病毒感染水平并不像在Huh 7细胞中观察到的那样大。在进一步的研究中，Hay、Patel和colleagyes在hESC-Heps中发现了强烈的III型干扰素应答，而在Huh 7细胞中并不明显。
In this study, human embryonic stem cell-derived hepatocytes (hESC-Heps) were investigated for their ability to support hepatitis C virus (HCV) infection and replication. hESC-Heps were capable of supporting the full viral life cycle, including the release of infectious virions. Although supportive, hESC-Hep viral infection levels were not as great as those observed in Huh7 cells. We reasoned that innate immune responses in hESC-Heps may lead to the low level of infection and replication. Upon further investigation, we identified a strong type III interferon response in hESC-Heps that was triggered by HCV. Interestingly, specific inhibition of the JAK/STAT signaling pathway led to an increase in HCV infection and replication in hESC-Heps. Of note, the interferon response was not evident in Huh7 cells. In summary, we have established a robust cell-based system that allows the in-depth study of virus-host interactions in vitro. hESC-derived hepatocytes support hepatitis C virus (HCV) infection and replication hESC-derived hepatocytes activate innate immunity in response to HCV infection Inhibition of JAK/STAT signaling improves HCV infection and replication Human embryonic stem cell-derived hepatocytes (hESC-Heps) were investigated for their ability to support hepatitis C virus (HCV) life cycle. Although supportive, hESC-Hep viral infection levels were not as great as those observed in Huh7 cells. Upon further investigation, Hay, Patel, and colleagyes identified a strong type III interferon response in hESC-Heps that was not evident in Huh7 cells.
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影响因子：
6
作者：
Medine, Claire N.;Lucendo-Villarin, Baltasar;Hay, David C.
通讯作者：
Hay, David C.
影响因子：
11.4
作者：
Scarselli, E;Ansuini, H;Vitelli, A
通讯作者：
Vitelli, A
影响因子：
13.5
作者：
Sullivan, Gareth J.;Hay, David C.;Park, In-Hyun;Fletcher, Judy;Hannoun, Zara;Payne, Catherine M.;Dalgetty, Donna;Black, James R.;Ross, James A.;Samuel, Kay;Wang, Gang;Daley, George Q.;Lee, Je-Hyuk;Church, George M.;Forbes, Stuart J.;Iredale, John P.;Wilmut, Ian
通讯作者：
Wilmut, Ian
影响因子：
56.9
作者：
Pileri, P;Uematsu, Y;Abrignani, S
通讯作者：
Abrignani, S
DOI：
10.1073/pnas.1121400109
发表时间：
2012-02-14
影响因子：
11.1
作者：
Schwartz, Robert E.;Trehan, Kartik;Bhatia, Sangeeta N.
通讯作者：
Bhatia, Sangeeta N.